METHODS:

Monkeys were treated with single or multiple topical treatments of 500 μg SNP or L-NAME to one eye. IOP was determined by Goldmann applanation tonometry, PD with vernier calipers in room light, Rfx by Hartinger coincidence refractometry, AHF by fluorophotometry, and MAP with a blood pressure monitor. OF was determined by two-level constant pressure perfusion following anterior chamber exchange.

RESULTS:

Following four topical treatments with 500 μg SNP, 30 minutes apart, IOP was significantly decreased from 2 to 6 hours compared with the contralateral control with the maximum IOP reduction of 20% at 3 hours (P < 0.001). PD, Rfx, and AHF were unchanged. Effects on MAP were variable. OF after SNP exchange was significantly increased by 77% (P < 0.05) at 10(-3) M. Topical L-NAME had no effect on IOP, PD, Rfx, or MAP.

CONCLUSIONS:

Enhancement of nitric oxide concentration at targeted tissues in the anterior segment may be a useful approach for IOP reduction for glaucoma therapy. Additional studies are warranted before conclusions can be made regarding the effect of NOS inhibition on ocular physiology in nonhuman primates.

IOP after topical SNP. Following a single treatment with 50 μg (A) or 500 μg (B) of SNP, IOP was decreased by 10% to 15% at various time points compared with vehicle-treated eyes. Four hourly treatments with 500 μg SNP (C) prolonged the IOP reduction, but this was not significantly different from the vehicle-treated eye except at the 3-hour time point. Treatment with 500 μg SNP at four 30-minute intervals (D) produced a significant 15% to 20% reduction in IOP that was sustained for several hours. *Significantly different from baseline prior to the first treatment (BL0) or §compared with the opposite eye, P < 0.05. ANOVA analysis showed a significant decrease in IOP in treated compared with control eyes following a single dose of 50 μg SNP ([A], P = 0.049), 500 μg SNP ([B], P = 0.035), and after treatment with 500 μg SNP at 30-minute intervals (four doses, [D], P < 0.0001). Results for 500 μg SNP at 1 hour intervals (four doses, [C]) approached significance (P = 0.054).

L-NAME effects on IOP, MAP, HR. Topical treatment with the NOS inhibitor L-NAME had no effect on IOP in treated compared with vehicle control eyes, although IOP in both eyes were significantly less than baseline at various time points. MAP and HR were also unaffected, although there was a tendency for HR to decrease with time as was seen after SNP in . *Significantly different from baseline prior to the first treatment (BL0), P < 0.05. ANOVA analysis showed no effect of L-NAME on IOP, MAP, or HR.